Precise and accurate delivery of drugs or therapeutic agents to a specific treatment site within a subject represents a substantial challenge in the design of drug delivery systems. Site-specific drug delivery can be particularly challenging when the drug is to be delivered to the subject long-term, e.g., over several hours to several days, weeks or months.
One approach to long-term site-specific drug delivery involves the use of implantable delivery systems, e.g., biodegradable or osmotically-driven drug delivery devices (see e.g., U.S. Pat. Nos. 5,607,696, 5,609,885, and 5,783,213. While these implantable systems avoid the need for repeated injections often associated with long-term drug therapy administration, they have a number of limitations. First, the treatment sites which they can access are limited. Second, sites to which drug delivery is required can be fragile, sensitive or inaccessible and thus often not amenable to insertion of an implant. Third, the size of the delivery device can be impractical for long-term treatment regimes as the reservoir of the device that holds the drug either needs to be large enough to hold sufficient quantities of drug for the course of treatment or, alternatively, allow re-filling with drug during the course of the treatment. The latter is especially troubling as manipulating, re-filling and re-positioning these implantable devices can have serious consequences, e.g., increased risk of infection, patient discomfort, and increased costs.
Difficulty in delivery of drugs or agents to inaccessible locations of the body has been addressed in part by the use of catheters attached to drug delivery devices. For example, the distal end of such a catheter can be positioned at the desired site of delivery in the body, with the catheter acting as a conduit for the drug or desired agent from the drug delivery device. This configuration allows access to previously inaccessible sites, but these devices face many of the same issues as the traditional drug delivery devices, such as catheter size and toxicity at the delivery site.
An alternative approach is to provide formulations having high concentrations of drug, such that delivery of small amounts of formulation are sufficient to provide for a desired therapeutic effect. The total amount of formulation required for long-term therapy is thus substantially decreased, thus minimizing the size requirements for the reservoir of the device used to accomplish delivery. While this approach has met with some success, there are still serious limitations for certain therapeutics and for chronic delivery. For example, formulations with high concentrations of drug can be toxic to cells at the delivery site, or can result in irritation, inflammation, and tissue damage at the delivery site. Often formulating drugs at such high concentrations requires the use of very high or very low pH solutions, which alone can cause adverse side effects, particularly at the delivery site.
There is thus a need in the field for drug delivery devices which allow the use of a smaller drug reservoir and highly concentrated drug formulations, and that provide for safe delivery to a treatment site for long-term therapy.